The present invention relates to a micro-catheter device utilizing xcexcJ electrical discharges for the dissolution of thrombus in blood vessels, and more particularly for such treatments in the small diameter circulatory arteries of the brain in victims of stroke. It further relates to a technique for electroacoustic wave propagation against thrombus contemporaneous with high-velocity projection or jetting of pharmacologic agents against thrombus, the combination of acoustic wave or mechanical effects with pharmacologic thrombolysis being adapted to cause rapid dissolution or depolymerization of fibrin in thrombus.
In the treatment of thrombus in a blood vessel, either in cardiac patients or stroke victims, conventional treatment is the intravenous administration of pharmacologic agents, such as t-PA (tissue plasminogen activator), streptokinase or urokinase. In such intravenous drug deliveries, the probability of success may be less than about 50 percent, and the success rates are limited by the fact that agents are not delivered directly to the site of the thrombus.
To ablate thrombus in an invasive procedure, various energy-based catheters have been developed, for example utilizing laser and ultrasound energy delivery systems. A disadvantage of such approaches is that the catheter diameter may be too large, and the catheter""s flexibility may be limited, thus preventing the working end of the catheter from reaching the thrombus site in the small circulatory arteries of the patient""s brain.
Another disadvantage of such catheters is the technique associated with positioning the catheter""s working end in close proximity to thrombus prior to energy delivery to have the desired effect. For example, in using a pulsed laser catheter for the ablation or photo-disruption of thrombus, the pioneering technique relied on the steady advance of the working end through the target lesion while continuously emitting pulsed laser energy. The photonic energy of the laser is absorbed by the thrombus if the working end is positioned properly. Investigators found that such laser treatment could cause excessive thermal effects and damage vessel walls.
More recently, the original laser-catheter technique has been modified to a xe2x80x9cpulse-and-retreatxe2x80x9d approach to reduce thermal effects. In other words, the laser pulses are commenced for a brief xe2x80x9csessionxe2x80x9d just before the working end reaches the target lesion, and then the pulsing is paused for about 60 seconds before advancing the working end for another lasing xe2x80x9csession.xe2x80x9d The pause is adapted to allow for cooling of the vessel walls and dissipation of any gas bubbles in blood caused by the pulsed laser treatment.
The disadvantages of such pulse-and-retreat techniques are that they are time-consuming, it is difficult to effectively position the working end in relation to the thrombus prior to the initial lasing session, and it is even more difficult to position the working end prior to follow-on lasing xe2x80x9csessions.xe2x80x9d (See, e.g., Topaz et al., xe2x80x9cAcute Results, Complications, and Effect of Lesion Characteristics on Outcome with the Solid-state, Pulsed Wave, Mid-Infrared Laser Angioplasty System,xe2x80x9d Lasers in Surg. and Med. 22:228-239 (1998). Further, some such laser angioplasty treatments generally rely on photothermal absorption within the high water content of the thrombus itself to disrupt the thrombus.
It would be preferable to not deliver such excessive thermal effects to intraluminal fluids and to the thrombus. In using ultrasound catheters for blood clot disruption, it is believed that an ultrasonic xe2x80x9cradiatorxe2x80x9d comprising a piezoelectric crystal or elongate tuned member cannot easily be miniaturized to the size needed for the brain""s circulatory arteries and still deliver significant acoustic power. (Cf. U.S. Pat. No. 5,318,014 to Carter titled xe2x80x9cUltrasonic Ablation/Dissolution Transducerxe2x80x9d).
What is needed is a micro-catheter and working end: (i) that can be miniaturized to be easily introduce into 1 mm to 3 mm brain circulatory arteries either independently or over a guidewire; (ii) that has a lumen together with pharmacologic agent dosimetry control means for controlled delivery of such agents directly to the thrombus site; (iii) that has pharmacologic agent pressure delivery means for creating pressure gradients for such agent delivery into the working end and against thrombus; (iv) that carries acoustic-energy generation means for delivering acoustic energy against thrombus; (v) that includes control systems for modulating all parameters of both pharmacologic agent delivery pressure and acoustic energy propagation; (vi) that protects the endothelium and vessel walls from thermal damage; (vii) that protects the endothelium and vessel walls from acoustic damage while at the same time dissolving thrombus; (viii) that can be activated in a continuous mode while advancing the working end toward and through the thrombus to require less precision in the imaging component of a thrombolysis procedure; (ix) that utilizes a non-complex energy source such as electrical discharge instead of a laser source or an ultrasound generator; and (x) that provides a system with disposables that are simple and inexpensive to manufacture.
The present invention comprises a micro-catheter system that utilizes pulsed electrical discharges between first and second electrodes disposed within a recessed bore of the catheter working end. The microjoule discharges are adapted to expand gas bubbles that rapidly collapse into a cavitating volume of an electrolytic fluid composition including a pharmacologic agent AG introduced into the working end from a computer-controlled source.
The expansion and collapse of such gas bubbles at a high repetition rate will create acoustic waves that propagate distally from the working end of the micro-catheter to disrupt thrombus. The expansion and collapse of such cavitation bubbles also will project or xe2x80x9cjetxe2x80x9d the pharmacologic agent at a controlled velocity into the acoustically disrupted thrombus to further depolymerize the thrombus allowing it to flow through the patient""s circulatory system.
The catheter system includes a computer-controller and various subsystems that allow for independent modulation of (i) all aspects of harmacologic agent delivery, and (ii) all parameters of electrical discharge to xe2x80x9ctailorxe2x80x9d the combined acoustic wave effects and pharmacologic agent effects to dissolve thrombus rapidly since the passage of time is critical in treating victims of stroke. It is believed that there are wide variations in thrombus size, location and other patient-specific characteristics that will require many different treatment parameters, which are offered by the control systems of the invention.
With respect to pharmacologic agent delivery, the system allows modulation of the dose of pharmacologic agent, the pressure or velocity of agent propagation into thrombus, and the timing of agent introduction relative to the actuation acoustic waves for disrupting the thrombus. With respect to the electrical discharge source, the computer controller and software can independently modulate voltage, peak power per pulse, discharge pulse length, the energy profile within each discharge pulse, and the timing between discharge pulses resulting in a set or variable discharge pulse rate.